Field of the Invention
This invention relates to sustained release formulations of dopaminergic compounds, including S-2-[(Benzylamino)-methyl]-2,3,8,9-tetrahydro-7H-1,4-dioxino[2,3-e]indol-8-one (aplindore) and pharmaceutically acceptable salts thereof.
Description of the Related Art
Compounds having the 2-(Aminomethyl)-2,3,8,9-7H-4-dioxino[2,3-e]-indol-8-one structure have been reported to have significant activity at the dopamine receptor, as well as the ability to modulate dopamine synthesis. See U.S. Pat. No. 5,756,532, incorporated by reference herein in its entirety for all purposes. These compounds are useful in the treatment and prevention of a variety of dopaminergic disorders including schizophrenia, schizoaffective disorder, symptoms of Parkinson's disease, Tourette's syndrome, psychosis in Lewis Body disease, psychosis in Alzheimer's disease, hyperprolactinemia, drug addiction and acute mania in bipolar disorder. The potent and selective D2/D3 partial agonist aplindore (S-2-[(Benzylamino)-methyl]-2,3,8,9-tetrahydro-7H-1,4-dioxino[2,3-e]indol-8-one) has been identified as a treatment for schizophrenic patients.
The administration of aplindore results in high initial drug concentrations. Such an “immediate release” pattern can pose difficulties, which include failure to maintain optimal exposure levels over time, and unpleasant side effects from having too large initial dose. Thus, there is a significant need for controlled release aplindore formulations capable of increasing Tmax and/or decreasing Cmax without reducing overall drug exposure. This invention is directed to these, as well as other, important ends.